Degenerative cardiovascular disease, atherosclerosis, accounts for more death and disability than any other disease that affects American people. The atherogenic process is thought to begin with the disruption of normal vascular endothelium. The response to this disruption in experimental animals is platelet adhesion to the subendothelium followed by myointimal thickening. If endothelial injury continues the myointimal thickening takes the form of a typical fibrous cap lesion of atherosclerosis. We wish to examine the role of the von Willebrand factor in the response to the initial injury and to determine if the endothelial repair process is affected by von Willebrand factor. To do this we will do three basic experiments each using normal pigs and with von Willebrand's disease. We will injure aortic endothelium with a balloon-tipped catheter and study the reaction using light and electron microscopy, immunohistologic methods for demonstration of tissue von Willebrand factor, and 3H-thymidine uptake in replicating cells. Secondly, we will expose pigs to low levels of carbon monoxide and study the effect on the vascular wall by the methods noted above. Finally, we will follow the development of coronary and aortic atherosclerosis in normal and bleeder pigs fed a diet high in cholesterol and fat. Results of these studies should provide information on the interaction of endothelium and platelets as mediated by the von Willebrand factor and therefore on the possible role of each in the development of atherosclerosis.